CpG oligodeoxynucleotide augments the antileishmanial activity of miltefosine against experimental visceral leishmaniasis

Abstract

Promising antileishmanial efficacy was observed in animals treated with liposomal CpG ODN and miltefosine, strongly supported by enhancement of Th1 cytokines as well as NO, ROS and H(2)O(2) levels. The correlation of experimental findings in both the models (mouse and hamster) strengthens the potential of CpG ODN as an immunomodulator in combination with miltefosine against VL.

CpG Oligodeoxynucleotide 2006 and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

“…The efficacy of this combination was comparable to the efficacy of the curative dose of miltefosine. It was observed that the efficacy profile of CpG-ODN-2006 corroborated with the efficacy of CpG-ODN-1826 observed in a previous study from our lab (18). In order to explore the effect of liposomal lipids on parasitic inhibition, an empty liposome preparation was also administered along with free and liposomal CpG-ODN (1 nM) in a separate experiment.…”

“…They also point to the therapeutic potential of CpG-ODN in redirecting curative Th1 responses in Th2-driven disorders. Previous work from our lab also strengthens the immunomodulatory role of CpG-ODN for treatment of VL (18). CpG-ODNs are a class of pharmacotherapeutic agents characterized by the presence of an unmethylated CG dinucleotide in specific base sequence contexts (CpG motif).…”

“…Liposomes containing CpG-ODN-2006 were prepared by the dehydration-rehydration vesicle (DRV) method (13,15,18).The lipid phase consisted of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (6 M) and cholesterol (2 M) dissolved in chloroform-methanol (2:1 [vol/vol]) in a flat-bottom tube. The solvent was removed by slow evaporation under nitrogen for deposition of a thin film of lipid on the tube surface.…”

“…The parasite inhibition observed at 40 mg/kg was 99.8%, followed by 92%, 80.3%, 55.5%, and 35.8% at doses of 20, 10, 5, and 2.5 mg/kg, respectively. The dose selected for the combination trial was 5 mg/kg, as it was subcurative and nontoxic (18). amastigotes/animal) and hamsters (1 ϫ 10 7 amastigotes/animal).…”

Antileishmanial efficacy of fluconazole and miltefosine in combination with an immunomodulator—picroliv

“…Cells were washed in incomplete medium by centrifugation at 1,000 rpm for 10 min and layered using complete medium in 24-well culture plates in a population of 1×10 6 per well. Cells were incubated with inhibitors (L-NAME, 10 μM; PTX, 10 μM; and NaN 3 , 10 μM) for 1 h at 37°C in 5% CO 2 followed by induction with PMA (20 μM) and incubation of 1 h at 37°C in 5% CO 2 (Sane et al 2010). Finally, 10 μM of dyes (DCFDA or DAF-2 DA) was added to each well and incubated for 30 min at 37°C in 5% CO 2 .…”